Role of mixtures of organic pollutants in the development of metabolic disorders via the activation of xenosensors

Environmental pollutants, particularly persistent organic pollutants but also widespread short-lived ones (bisphenol family and phthalates), also may be endocrine disruptors. These molecules are emerging in the etiology of the world-wide epidemic of chronic diseases such as obesity, diabetes and the metabolic syndrome. These pollutants mainly bind either xenosensors or endocrine receptors, which then act as transcription factors. On the one hand, recent epidemiological studies have pinpointed the association between human exposure to mixtures of such contaminants and metabolic disorders. On the other hand, numerous studies in animal and in vitro models have described the consequences of exposure to individual pollutants in terms of modifications of the transcriptome or the metabolome implicating diverse signaling and metabolic pathways linked to obesity or the metabolic syndrome. The objectives of this commentary are 1) to give an overview of the potential role of organic pollutant mixtures on metabolic dysfunction, with a focus on obesity, type 2 diabetes and the metabolic syndrome in humans, as assessed by epidemiological studies; 2) to assess the state of art of in vitro and in vivo models to address this question, since most studies focus on the effects of single pollutants and 3) to evaluate the limits of the various models, in relation to the epidemiological studies